Department of Chemical and Biochemical Engineering, Rutgers University, 98 Brett Road, Piscataway, NJ, 08854, USA.
Department of Biomedical Engineering, Rutgers University, 599 Taylor Road, Piscataway, NJ, 08854, USA.
Adv Healthc Mater. 2019 Jan;8(2):e1801044. doi: 10.1002/adhm.201801044. Epub 2018 Dec 17.
Global increases in life expectancy drive increasing demands for bone regeneration. The gold standard for surgical bone repair is autografting, which enjoys excellent clinical outcomes; however, it possesses significant drawbacks including donor site morbidity and limited availability. Although collagen sponges delivered with bone morphogenetic protein, type 2 (BMP2) are a common alternative or supplement, they do not efficiently retain BMP2, necessitating extremely high doses to elicit bone formation. Hence, reports of BMP2 complications are rising, including cancer promotion and ectopic bone formation, the latter inducing complications such as breathing difficulties and neurologic impairments. Thus, efforts to exert spatial control over bone formation are increasing. Several tissue engineering approaches have demonstrated the potential for targeted and controlled bone formation. These approaches include biomaterial scaffolds derived from synthetic sources, e.g., calcium phosphates or polymers; natural sources, e.g., bone or seashell; and immobilized biofactors, e.g., BMP2. Although BMP2 is the only protein clinically approved for use in a surgical device, there are several proteins, small molecules, and growth factors that show promise in tissue engineering applications. This review profiles the tissue engineering advances in achieving control over the location and onset of bone formation (spatiotemporal control) toward avoiding the complications associated with BMP2.
全球预期寿命的增长推动了对骨再生的需求不断增加。手术骨修复的金标准是自体移植物，它具有出色的临床效果；然而，它也存在显著的缺点，包括供体部位发病率和有限的可用性。虽然与骨形态发生蛋白 2（BMP2）一起递送的胶原海绵是一种常见的替代物或补充物，但它们不能有效地保留 BMP2，需要极高的剂量才能引发骨形成。因此，BMP2 并发症的报告不断增加，包括癌症促进和异位骨形成，后者会引起呼吸困难和神经损伤等并发症。因此，人们努力对骨形成进行空间控制。几种组织工程方法已经证明了靶向和控制骨形成的潜力。这些方法包括源自合成来源的生物材料支架，例如磷酸钙或聚合物；天然来源，例如骨或贝壳；以及固定化生物因子，例如 BMP2。尽管 BMP2 是唯一一种在手术器械中临床批准使用的蛋白质，但有几种蛋白质、小分子和生长因子在组织工程应用中显示出了前景。本综述介绍了在实现对骨形成位置和起始的控制（时空控制）方面的组织工程进展，以避免与 BMP2 相关的并发症。
